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Neocerebellar Crus I abnormalities associated with a speech and language disorder due to a mutation in FOXP2

Argyropoulos, GPD; Watkins, KE; Belton- Pagnamenta, E; Liégeois, FJ; Saleem, KS; Mishkin, M; Vargha-Khadem, F; (2019) Neocerebellar Crus I abnormalities associated with a speech and language disorder due to a mutation in FOXP2. The Cerebellum 10.1007/s12311-018-0989-3. (In press). Green open access

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Abstract

Bilateral volume reduction in the caudate nucleus has been established as a prominent brain abnormality associated with a FOXP2 mutation in affected members of the ‘KE family’, who present with developmental orofacial and verbal dyspraxia in conjunction with pervasive language deficits. Despite the gene’s early and prominent expression in the cerebellum and the evidence for reciprocal cerebellum-basal ganglia connectivity, very little is known about cerebellar abnormalities in affected KE members. Using cerebellum-specific voxel-based morphometry (VBM) and volumetry, we provide converging evidence from subsets of affected KE members scanned at three time points for grey matter (GM) volume reduction bilaterally in neocerebellar lobule VIIa Crus I compared with unaffected members and unrelated controls. We also show that right Crus I volume correlates with left and total caudate nucleus volumes in affected KE members, and that right and total Crus I volumes predict the performance of affected members in non-word repetition and non-verbal orofacial praxis. Crus I also shows bilateral hypo-activation in functional MRI in the affected KE members relative to controls during non-word repetition. The association of Crus I with key aspects of the behavioural phenotype of this FOXP2 point mutation is consistent with recent evidence of cerebellar involvement in complex motor sequencing. For the first time, specific cerebello-basal ganglia loops are implicated in the execution of complex oromotor sequences needed for human speech.

Type: Article
Title: Neocerebellar Crus I abnormalities associated with a speech and language disorder due to a mutation in FOXP2
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s12311-018-0989-3
Publisher version: https://doi.org/10.1007/s12311-018-0989-3
Language: English
Additional information: © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/).
Keywords: FOXP2, Verbal dyspraxia, Cerebellum, Caudate nucleus, MRI, VIIa crus I
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Developmental Neurosciences Prog
URI: http://discovery.ucl.ac.uk/id/eprint/10061519
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